@article {9641,
	title = {A comparative study of structural variant calling in WGS from Alzheimer{\textquoteright}s disease families.},
	journal = {Life Sci Alliance},
	volume = {7},
	year = {2024},
	month = {2024 May},
	abstract = {<p>Detecting structural variants (SVs) in whole-genome sequencing poses significant challenges. We present a protocol for variant calling, merging, genotyping, sensitivity analysis, and laboratory validation for generating a high-quality SV call set in whole-genome sequencing from the Alzheimer{\textquoteright}s Disease Sequencing Project comprising 578 individuals from 111 families. Employing two complementary pipelines, Scalpel and Parliament, for SV/indel calling, we assessed sensitivity through sample replicates (N = 9) with in silico variant spike-ins. We developed a novel metric, D-score, to evaluate caller specificity for deletions. The accuracy of deletions was evaluated by Sanger sequencing. We generated a high-quality call set of 152,301 deletions of diverse sizes. Sanger sequencing validated 114 of 146 detected deletions (78.1\%). Scalpel excelled in accuracy for deletions <=100 bp, whereas Parliament was optimal for deletions >900 bp. Overall, 83.0\% and 72.5\% of calls by Scalpel and Parliament were validated, respectively, including all 11 deletions called by both Parliament and Scalpel between 101 and 900 bp. Our flexible protocol successfully generated a high-quality deletion call set and a truth set of Sanger sequencing-validated deletions with precise breakpoints spanning 1-17,000 bp.</p>},
	keywords = {Alzheimer Disease, Humans, Whole Genome Sequencing},
	issn = {2575-1077},
	doi = {10.26508/lsa.202302181},
	author = {Malamon, John S and Farrell, John J and Xia, Li Charlie and Dombroski, Beth A and Das, Rueben G and Way, Jessica and Kuzma, Amanda B and Valladares, Otto and Leung, Yuk Yee and Scanlon, Allison J and Lopez, Irving Antonio Barrera and Brehony, Jack and Worley, Kim C and Zhang, Nancy R and Wang, Li-San and Farrer, Lindsay A and Schellenberg, Gerard D and Lee, Wan-Ping and Vardarajan, Badri N}
}
